Lactones bridged-ring

Lactones by ring expansion of lactols. Medium-sized lactones can be obtained in reasonable yield by photolysis of the hypoiodites of catacondensed lactols, which results in regioselective cleavage of the bridging bond. The substrates are available by the general route shown for the 6/6 lactol 1, which is cleaved to the 10-membered lactone 2. This cleavage can be used for preparation of 9-membered... 

The conformational kinetic control of the chiral centres present in a molecule may be exemplified by the rran -diaxial opening of an epoxide i rf a polycyclic system [7]. In this case, the less stable conformation is also "frozen" by forming an auxiliary lactone bridge, which reverses temporarily the conformations of the rings and the substituents. 

As mentioned earlier in the discussion of cyclizations leading to (3-lactones, the (3-lactones formed from halolactonization of 1,4-dihydrobenzoic acids readily rearrange to produce bridged ring y-lac-tones.19 In some cases, the substitution pattern favors formation of the y-lactone even under conditions of kinetic control (equation 23).20 Synthesis of a variety of y-lactones by iodolactonization of dihydroben-zoic acid derivatives has been reported recently by Hart (equation 24).91 Attempted iodolactonization of the acid in the case where R = H resulted primarily in an oxidative decarboxylation however, iodolactonization was effected using the amide derivative. 

The mechanism of the atroposelective ring opening of a lactone-bridged biaryl, dinaphtho[2,l-t l, 2 -< ]oxepin-3(5//)-one, with a chiral oxazaborolidine-BH3 complex (Scheme 2) was studied using semi-empirical AMI calculations <2000JOC2517>. 

This predicted conformation is supported by SAR studies performed in a series of compounds in which the torsion angle of the bond between the aryl and the 1,4-dihydropyridine ring is fixed by lactone bridges of different chain lengths [5], and also by X-ray analysis [6]. 

Finally, after ester hydrolysis, HC1 decarboxylates the product and removes the protecting group. As we saw earlier, it is not easy to get a trans-fused 5/6 system. In this sequence the molecule is effectively tricked into making the trans ring junction by the work done with the blocking lactone bridge. 

Rearrangement. An entry into the trichothecane nucleus from a fused ring portion to the bridged ring system is based on ionization of the allylic lactone that triggers a C-C bond migration. The product is a synthetic precursor of verrucarol. 

Epoxide 109 is opened with Me3SiBr (Ph3P-catalysed) and another elimination with DBU gives the allylic alcohol 117. The epoxidation that follows is controlled in a couple of ways. Firstly, the axial alcohol can direct the reagent (the same peroxyacid used to make 109) to the bottom face of the six-membered ring which is also the less hindered side of the molecule (opposite the lactone bridge) 118. The synthesis is completed with basic methanolysis of the lactone 118 to give racemic methyl shikimate 116. 

Finally, DcTar has studied the lactonization of hydroxy acids in bridged ring systems, with the aid of hydrocarbon models (DeTar, 1974 a,b). The calculated and experimental rates show a reasonable correlation. 

For synthetic organic chemists, the schemes are self-explanatory and require no detailed comment. In strobilurins, the ortho substitution pattern at the central bridging ring favors the use of easy accessible starting materials or intermediates in which a lactone-type ring is cleaved to obtain pharmacophores and side chains built up in the proper ortho connection. As already mentioned at the end of Section 13.2.3.4, the thermodynamically favored E-configuration of the differ-... 

Antimalarial activity Unsaturated lactone on ring A, oxymethyl bridge between C-8 and C-11 [63]... 

Floresolide B (160), a recently discovered natural product isolated from an ascidian of genus ApJidiwm that exhibits cytotoxicity against KB tumor cells, contains an aromatic ring connected to a [10]-metacyclophane and a seven-membered ring lactone. The lactone bridge present in substrate 158 was installed prior to the... 

Structures in which one or more (but not all) rings of an aggregate are lactone rings are named by placing -carbolactone (denoting the —O—CO— bridge) after the names of the structures that... 

Annotinine, C gHjjOjN, (1). M.p. 232° perchlorate, m.p. 267°. In a later paper (1947) Manske and Marion record the results of the action of alkali and of halogen acids on annotinine, and of the oxidation of the base and discuss the reaction products. They conclude that two of the oxygen atoms are present as a lactone group and that the third oxygen may form an ether bridge in a 5- or 6-membered ring. 

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